Molecular Imaging of Inflammation in Osteoarthritis Using a Water-Soluble Fluorocoxib.

Autor:	Uddin MJ; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Vemulapalli A; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Niitsu H; Department of Medicine, and Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Crews BC; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Oltman CG; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Kingsley PJ; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Kavanaugh TE; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States., Bedingfield SK; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States., Mcintyre JO; Department of Cancer Biology, Vanderbilt Institute of Imaging Science, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Milad M; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Aleem AM; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States., Coffey RJ; Department of Medicine, and Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States., Duvall CL; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232, United States., Marnett LJ; A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Feb 24; Vol. 11 (10), pp. 1875-1880. Date of Electronic Publication: 2020 Feb 24 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.9b00512
Abstrakt:	Clinical imaging approaches to detect inflammatory biomarkers, such as cyclooxygenase-2 (COX-2), may facilitate the diagnosis and therapy of inflammatory diseases. To this end, we report the discovery of N -[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1 H -indol-3-yl]acetamide chloride salt (fluorocoxib D), a hydrophilic analog of fluorocoxib A. Fluorocoxib D inhibits COX-2 selectively in purified enzyme preparations and cells. It exhibits adequate photophysical properties to enable detection of COX-2 in intact cells, in a mouse model of carrageenan-induced acute footpad inflammation and inflammation in a mouse model of osteoarthritis. COX-2-selectivity was verified either by blocking the enzyme's active site with celecoxib or by molecular imaging with nontargeted 5-carboxy-X-rhodamine dye. These data indicate that fluorocoxib D is an ideal candidate for early detection of inflammatory or neoplastic lesions expressing elevated levels of COX-2. Competing Interests: The authors declare no competing financial interest.
Databáze:	MEDLINE
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